School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
Biochem Pharmacol. 2011 Apr 1;81(7):825-37. doi: 10.1016/j.bcp.2011.01.003. Epub 2011 Jan 15.
A key part of the innate immune system is a network of pattern recognition receptors (PRRs) and their associated intracellular signalling pathways. Toll-like receptors (TLRs) are one such group of PRRs that detect pathogen associated molecular patterns (PAMPs). Activation of the TLRs with their respective agonists results in the activation of intracellular signalling pathways leading to the expression of proinflammatory mediators and anti-microbial effector molecules. Activation of the innate immune system through TLRs also triggers the adaptive immune response, resulting in a comprehensive immune program to eradicate invading pathogens. It is now known that immune surveillance and inflammatory responses occur in the central nervous system (CNS). Furthermore it is becoming increasingly clear that TLRs have a role in such CNS responses and are also implicated in the pathogenesis of a number of conditions in the CNS, such as Alzheimer's, stroke and multiple sclerosis. This is likely due to the generation of endogenous TLR agonists in these conditions which amplifies a detrimental neurotoxic inflammatory response. However TLRs in some situations can be neuroprotective, if triggered in a favourable context. This review aims to examine the recent literature on TLRs in the CNS thus demonstrating their importance in a range of infectious and non-infectious diseases of the brain.
先天免疫系统的一个关键部分是模式识别受体 (PRRs) 及其相关的细胞内信号通路网络。Toll 样受体 (TLRs) 就是这样一组 PRRs，它们可以识别病原体相关的分子模式 (PAMPs)。TLRs 与其各自的激动剂结合可激活细胞内信号通路，导致促炎介质和抗微生物效应分子的表达。通过 TLR 激活先天免疫系统还会引发适应性免疫反应，从而产生一个全面的免疫程序来消灭入侵的病原体。现在已知免疫监视和炎症反应发生在中枢神经系统 (CNS) 中。此外，越来越明显的是，TLRs 在这些 CNS 反应中起作用，并且也与 CNS 中的许多疾病的发病机制有关，如阿尔茨海默病、中风和多发性硬化症。这可能是由于这些情况下内源性 TLR 激动剂的产生放大了有害的神经毒性炎症反应。然而，在某些情况下，如果在有利的情况下触发 TLRs，它们也可以起到神经保护作用。这篇综述旨在研究 CNS 中 TLR 的最新文献，从而证明它们在一系列感染性和非传染性脑部疾病中的重要性。
